The present invention relates to a process for the preparation of indoles by cyclisation of phenylhydrazones, which are formed from phenylhydrazine and ketones, in the presence of less than 5 equivalents of an acid compound having a pK value of 1.3-4.5.
Indoles are important intermediates in the dyestuffs industry. It is known to cyclise phenylhydrazones in organic media using Lewis acids or protonic acids, for example in ethanol in the presence of zinc chloride (Chem.-Zeitg. 22 (1898), 38), in glacial acetic acid as the reaction medium (J. Org. Chem. 42 (1977), 2474) or in chloroform in the presence of polyphosphoric acid esters (Chem. and Ind. 1965, 473). Furthermore, a reaction of this type in polyphosphoric acid without further addition of solvent has been described (J. Am. Chem. Soc. 74 (1952), 3948).
It is also known to carry out this reaction in an aqueous medium using Broensted acids, in which case, however, an acid having a pK value of below 1.3 has to be employed (German Offenlegungsschrift 19 06 832; J. Org. Chem. 33 (1968), 4283).
It has now been found, surprisingly, that the indole synthesis in an aqueous reaction medium can also be carried out in short reaction times with good yields using acid compounds having a pK value of 1.3 and above, less than 5 equivalents of this acid compound, relative to the phenylhydrazine, being employed. This is the more surprising since it is known from German Offenlegungsschrift 19 06 832 that when substituted aliphatic or aromatic acids having a pK value in the vicinity of 1.3 are used large amounts of acid and long reaction times are required in order to achieve satisfactory yields.